Brca2 C-terminus interacts with Rad51 and contributes to nuclear focus formation in double-strand break repair of DNA
Brca2 C-terminus interacts with Rad51 and contributes to nuclear focus formation in double-strand break repair of DNA
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DOI：
10.2220/biomedres.25.269
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发表时间：
2004-12-01
影响因子：
1.2
通讯作者：
Hashizume, Kazuyoshi
中科院分区：
文献类型：
--
作者：
Ochiai, Kazuhiko;Morimatsu, Masami;Hashizume, Kazuyoshi
在人类和小鼠中，乳腺癌易感蛋白 BRCA2 和 RAD51 重组酶之间的相互作用对于通过同源重组进行 DNA 修复至关重要，该过程的失败可能导致癌症。 BRCA2 突变的细胞对电离辐射 (IR) 高度敏感，并且表现出 DNA 修复缺陷。使用酵母和哺乳动物双杂交测定，我们证明犬 Rad51 蛋白与犬 Brca2 的 C 末端特异性相互作用。为了支持这种相互作用的生物学意义，我们发现 COS-7 细胞中辐射诱导的 Rad51 焦点形成受到犬 Brca2 C 末端的强制表达的损害。小鼠 C 末端也获得了类似的结果。这些数据表明犬 Brca2 的 C 末端结构域具有结合 Rad51 的功能，并且该结构域有助于 IR 诱导的体内 Rad51 复合物的组装。
In humans and mice, the interaction between the breast cancer susceptibility protein, BRCA2, and RAD51 recombinase is essential for DNA repair by homologous recombination, the failure of this process can predispose to cancer. Cells with mutated BRCA2 are hypersensitive to ionizing radiation (IR) and exhibit defective DNA repair. Using yeast and mammalian two-hybrid assays, we demonstrate that canine Rad51 protein interacts specifically with the C-terminus of canine Brca2. In support of the biological significance of this interaction, we found that radiation-induced focus formation of Rad51 in COS-7 cells was compromised by forced expression of the C-terminus of canine Brca2. A similar result was obtained for the murine C-terminus. These data suggest that the C-terminal domain of canine Brca2 functions to bind Rad51 and that this domain contributes to the IR-induced assembly of the Rad51 complex in vivo.